Multivitamin restriction increases adiposity and disrupts glucose homeostasis in mice

Abstract

A strong association between obesity and low plasma concentrations of vitamins has been widely reported; however, the causality of this relationship is still not established. Our goal was to evaluate the impact of a multivitamin restriction diet (MRD) on body weight, adiposity and glucose homeostasis in mice. The mice were given a standard diet or a diet containing 50 % of the recommended vitamin intake (MRD) for 12 weeks. At the end of the experiment, total body weight was 6 % higher in MRD animals than in the control group, and the adiposity of the MRD animals more than doubled. The HOMA-IR index of the MRD animals was significantly increased. The adipose tissue of MRD animals had lower expression of mRNA encoding adiponectin and Pnpla2 (47 and 32 %, respectively) and 43 % higher leptin mRNA levels. In the liver, the mRNA levels of Pparα and Pgc1α were reduced (29 and 69 %, respectively) in MRD mice. Finally, the level of β-hydroxybutyrate, a ketonic body reflecting fatty acid oxidation, was decreased by 45 % in MRD mice. Our results suggest that MRD promotes adiposity, possibly by decreasing adipose tissue lipolysis and hepatic β-oxidation. These results could highlight a possible role of vitamin deficiency in the etiology of obesity and associated disorders.

Fig. 1

Multivitamin restriction increases body weight and adiposity. a Body weight evolution was followed during the 12 weeks of treatment. b Before killing, animal weight was established. c At the time of killing, after 12 weeks of treatment, adipose tissues (epididymal, subcutaneous and peri-renal) were weighed for each animal (n = 10). d The fat mass is reported relative to the total body weight of the animal. e An adiposity index was calculated by calculating the ratio between total fat mass and body weight for the animal. f Mean food intake was determined together with energy intake. g White bars correspond to mice submitted to the standard diet (SD), and black bars correspond to mice submitted to the multivitamin-restricted diet. Values are presented as the mean ± SEM. Bars not sharing the same letter are significantly different, p < 0.05

Fig. 2

Multivitamin restriction modifies AdipoQ and Lep expression in adipose tissue. a, b Gene expression in white adipose tissue is expressed relative to 18S ribosomal RNA levels in mice submitted to a standard diet (white bars) and multivitamin-restricted diet (black bars) for 12 weeks (n = 10). Values are presented as the mean ± SEM. Bars not sharing the same letter are significantly different, p < 0.05

Fig. 3

Multivitamin restriction increases fasted insulinemia and HOMA-IR. a, b Insulin and glucose levels were measured after overnight fasting in the plasma of mice that received the standard diet (white bars) or multivitamin-restricted diet (black bars) for 12 weeks (n = 10). c The HOMA-IR index was calculated based on glycemia and insulinemia. Values are presented as the mean ± SEM. Bars not sharing the same letter are significantly different, p < 0.05

Fig. 4

Multivitamin restriction decreases gene expression in the liver and white adipose tissue and β-hydroxybutyrate levels in plasma. Gene expression relative to 18S ribosomal RNA levels in the liver (a) and in white adipose tissue (b) of mice (n = 10) submitted to the standard diet (white bars) and multivitamin-restricted diet (black bars) for 12 weeks. c β-Hydroxybutyrate concentration in plasma of mice (n = 10) submitted to the standard diet (white bars) and multivitamin-restricted diet (black bars) for 12 weeks. Values are presented as the mean ± SEM. Bars not sharing the same letter are significantly different, p < 0.05